• Female or male patients, ≥18 years of age.

• Signed, written, informed consent.

• AJCC Stage IV \[any T, any N, M1d (0) or M1D(1)\] histologically confirmed cutaneous, acral or mucosal unresectable melanoma or unknown primary melanoma and at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm, measurable per RECIST version 1.1 guidelines (modified for brain metastases, enabling up to 5 target lesions in the brain as well as up to 5 extracranial target lesions). There is no upper limit restriction in the number of brain metastases, provided the remaining eligibility criteria are met.

• The BRAF mutation status must be available prior to randomisation.

• The treating clinician(s) should consider the intracranial disease amenable to stereotactic radiotherapy over whole brain radiotherapy. Patients for whom there is a definite and immediate indication for radiotherapy (e.g. rapidly progressing disease with associated clinical signs and /or symptoms) should not be considered for enrolment.

• Brain metastases must be untreated with any modality of radiotherapy or systemic treatment. Previous surgery for melanoma brain metastases is permitted if it resulted in gross total resection and no radiotherapeutic cavity boost was required.

• No prior systemic treatment for brain metastases is permitted unless given in the neoadjuvant or adjuvant settings for systemic drug the treatment for extracranial disease only. At the time of neoadjuvant or adjuvant systemic therapy for extracranial disease, there should be radiological evidence of the absence of brain metastases. The presenting diagnosis of brain metastases at the time of enrolment in this study must have occurred a minimum of 6 months after stopping neoadjuvant or adjuvant systemic therapy (prior anti PD1, anti PD-L1, anti CTLA-4, BRAF / MEK inhibitors or clinical trial agents) are acceptable in the setting of neoadjuvant or adjuvant treatment

• Asymptomatic from brain metastases at the time of study enrolment without corticosteroids, analgesia or any other treatment for the management of neurological symptoms (with the exception of antiepileptics prescribed for any reason, provided patient is asymptomatic). Resolved neurological symptoms are permitted if complete resolution, without any intervention, has been sustained for a minimum of 7 days prior to randomisation.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

⁃ A life expectancy \> 30 days.

⁃ Able to undergo MRI with Gadolinium contrast agent. CT of the brain is not an acceptable alternative should patients be unable to safely undergo a contrast MRI.

⁃ Adequate haematological, hepatic and renal organ function as defined by:

∙ White cell count ≥ 2.0 × 10x9/L

‣ Neutrophil count ≥ 1.5 × 10x9/L

‣ Haemoglobin ≥ 90 g/L

‣ Platelet count ≥ 100 x 10x9/L

‣ Total bilirubin ≤ 1.5 x ULN

‣ Alanine transaminase ≤ 3.0 x ULN

‣ Aspartate aminotransferase ≤ 3.0 x ULN

‣ Serum creatinine ≤ 1.5 x the upper limit of normal (ULN). If serum creatinine is \> 1.5 x ULN, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be 40ml/min to be eligible.

⁃ Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 23 weeks \* after the last dose of study treatment. Effective contraception includes:

∙ Intrauterine device with a documented failure rate of less than 1% per year.

‣ Vasectomised partner who is sterile prior to the female partner patient's commencement of study treatment and is the sole sexual partner for that female.

‣ Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associated with inhibition of ovulation.

⁃ Women who are not of childbearing potential are defined as any female who has had a documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation or any female who is post-menopausal (≥ one year without menses and \>50 years of age in the absence of hormone replacement therapy).

⁃ Men with any female partner of childbearing potential must agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 31 weeks\* after the last dose of study treatment. Effective contraception includes:

∙ Documented vasectomy and sterility

‣ In the partner - intrauterine device with a documented failure rate of less than 1% per year

‣ In the female partner - Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associated with inhibition of ovulation.

• These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.