• Age ≥ 18 years at the time of informed consent.

• Provide written informed consent and comply with the study protocol as judged by the Investigator. Of note, If the subject has an impairment that prevents him/her from providing written consent, the site may follow local institutional procedures for obtaining consent.

• Histologically confirmed diagnosis of cutaneous melanoma with radiographically confirmed metastases to the brain.

• Must have a tumor with known RAS, BRAF, and NF1 mutation status using a validated testing method prior to enrollment.

‣ Cohort A: RAS, BRAF, NF1, or triple wildtype

⁃ Cohort B: BRAF V600E or BRAF V600K

• Must have at least 1 untreated (no prior resection or radiation of the target lesion) parenchymal brain metastasis with minimal dimensions of ≥ 0.5 cm diameter and maximal dimensions ≤ 4 cm diameter, measured from a gadolinium enhanced MRI T1 sequence.

‣ Note: Subject may have received prior resection or radiation therapy for prior brain metastases.

• Must have received at least 1 line of prior systemic immunotherapy.

• For Cohort B, may have received 1 or more lines of prior BRAF or MEK inhibitor therapy.

• An ECOG Performance Status of 0 or 1, or Karnofsky score \>= 70

• Adequate bone marrow, organ function and laboratory parameters:

‣ ANC ≥ 1.5 × 109/L;

⁃ Hemoglobin ≥ 9 g/dL with or without transfusions;

⁃ Platelets ≥100,000/mm2;

⁃ AST and ALT ≤ 2.5 × ULN; in patients with liver metastases ≤ 5 × ULN;

⁃ Total bilirubin ≤ 1.5 × ULN; NOTE: Patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled

⁃ Serum creatinine ≤ 1.5 × ULN; OR calculated creatinine clearance \> 50 mL/min by Cockcroft-Gault formula; OR estimated glomerular filtration rate \> 50 mL/min/1.73m2.

⁃ International normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (aPTT) as follows:

∙ In the absence of therapeutic intent to anticoagulate the patient:

⁃ INR \< 1.5 × ULN.

• PT \< 1.5 × ULN.

• aPTT \< 1.5 × ULN.

• Adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.

• For women (any individual assigned female at birth) who are not postmenopausal (ie, \< 2 years after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active, must have a negative serum pregnancy test and agree to use a highly effective method of contraception for the duration of the study and for 90 days following the last dose of study drug.

• Male patients (any individual assigned male at birth) of reproductive potential must avoid pregnancy in partners who are women of childbearing potential, and such partners should not consider getting pregnant during the study and for at least 90 days after treatment is discontinued or longer if requested by local authorities. Male patients are considered to be of reproductive potential unless permanently sterile by bilateral orchidectomy or vasectomized with appropriate post-vasectomy documentation of absence of sperm in ejaculate.

• Adequate recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator. Exceptions include alopecia and peripheral neuropathy grade ≤ 2.