• Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible.

• Participants must have surgically accessible disease.

• Prior Therapy:

∙ The participant must have received at least one prior therapy at the time of initial diagnosis.

‣ Relapsed medulloblastoma or relapsed ependymoma are eligible.

‣ Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines

⁃ Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration.

• Monoclonal antibody treatment: \> 21 days prior to registration.

• Bevacizumab participants must have received last dose \> 21 days prior to study registration

• Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study.

• Radiation - Participants must have:

∙ Had their last fraction of local irradiation to primary tumor \>= 12 weeks prior to registration.

‣ Had their last fraction of craniospinal irradiation or total body irradiation \>= 12 weeks prior to registration

‣ At least 14 days after local palliative radiation (small-port)

• Age \>=12 months to \<= 39 years of age.

• Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>= 50 for participants \<= 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

• Corticosteroids: Participants who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.

• Organ Function Requirements (within 7 days prior to study registration)

∙ Adequate Bone Marrow Function Defined as:

⁃ Peripheral absolute neutrophil count (ANC) \>= 750/mm\^3

• Platelet count \>= 75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

• Hemoglobin \>= 8 g/dl.

‣ Adequate Renal Function Defined as:

⁃ Creatinine clearance or radioisotope GFR \>= 70 milliliter/minute (mL/min) /1.73 m\^2 or

• A serum creatinine based on age/sex as follows:

∙ Age / Maximum Serum Creatinine (mg/dL) Male / Maximum Serum Creatinine (mg/dL) Female.

• 1 to \< 2 years / 0.6 / 0.6.

• \>= 16 years / 1.7 / 1.4.

• \- The threshold creatinine values in this table were derived from the Schwartz formula for estimating Glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC) (Schwartz GJ and Gauthier B 1985).

‣ Adequate Liver Function Defined as:

⁃ Total Bilirubin \<= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN.

• Alanine aminotransferase (ALT) \<= 3x ULN.

• Aspartate aminotransferase (AST) \<= 3x ULN.

⁃ The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect pregnancy while participating in this study, the treating physician should be informed immediately.

⁃ Adequate neurologic function defined as participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.

⁃ Participants must enroll on the Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies (PNOC COMP) study if PNOC COMP is open to accrual at the enrolling institution

⁃ A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.