Tinostamustine With or Without Radiation Therapy in Treating Patients With Newly Diagnosed MGMT-Unmethylated Glioblastoma

Inclusion Criteria: * Be willing and able to provide written informed consent for the trial. * Have histologically confirmed World Health Organization grade IV glioma (glioblastoma \[GB\] or gliosarcoma). * Patients must have preliminary glioblastoma (GBM) MGMT status (tumor must be MGMT promoter unmethylated) determined prior to study entry. If initial MGMT status is determined to be "unmethylated", by an outside institution the patient may be enrolled and begin treatment. However, MGMT status must be retested following enrollment by central laboratory Clinical Laboratory Improvement Act (CLIA) certified testing at MD Anderson, if tissue is available. Confirmed IDH wildtype. The presence of an IDH mutation will be an exclusionary criteria for trial enrollment. * Have a performance status of \>= 60 on the Karnofsky performance scale (KPS). * If patient is on steroids, patient must be on a stable or decreasing dose of steroids for at least 5 days at the time of baseline brain magnetic resonance imaging (MRI). * Absolute neutrophil count (ANC) \>= 1,500 /mcL (within 14 days \[+3 working days\] of treatment initiation). * Platelets \>= 100,000 /mcL (within 14 days \[+3 working days\] of treatment initiation). * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days \[+3 working days\] of treatment initiation). * Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[C…