Willingness to return to Mayo Clinic for follow-up (during the active monitoring phase of the study) Willing to return to enrolling institution for follow-up or have a local physician willing to submit response and outcome data; Note: any and all therapy, potentially in its entirety, may be conducted outside of the Mayo Clinic Must be willing to return to Mayo Clinic enrolling institution for follow-up. Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136 Willingness to return to Mayo Clinic Rochester or another participating institution for follow-up; patients who are randomized to Arm B (cytotoxic chemotherapy) may receive chemotherapy at any oncology clinic able to provide the protocol-directed therapy and willing to send laboratory data to the participating institution; however, patients must be willing to return to the participating institution every two months for evaluation; patients who are randomized to Arm A must be willing to receive all treatment and follow-up at a participating institution Planned radiation treatments at Mayo Clinic Rochester Willing to undergo craniotomy and resection of their glioblastoma at Mayo Clinic Willingness to return to Mayo Clinic in Rochester, Minnesota for follow-up Willingness to return to Mayo Clinic in Rochester, Minnesota for follow-up Central pathology review to determine evaluability of archived esophagogastroduodenoscopy (EGD)/biopsy sample\r\n* NOTE: If archived sample was collected > 8 weeks prior to pre-registration (reg), is not available in a timely manner, or was collected outside of Mayo Clinic and considered unevaluable, then baseline EGD with primary tumor biopsy at Mayo Clinic must be performed unless clinically contraindicated; patient is allowed to enroll regardless of whether this Mayo Clinic tissue sample is evaluable; (only 1 EGD with primary tumor biopsy performed at Mayo Clinic =< 8 weeks prior to pre-reg is required)\r\n* NOTE: For both archival or newly obtained tissue, only biopsies are adequate (fine needle aspiration [FNA] is not adequate) Willingness to return to Mayo Clinic Rochester for follow-up Willing to return to Mayo Clinic for follow-up Willingness to return to the Mayo Clinic enrolling institution for follow-up Willing to return to Mayo Clinic Rochester for follow-up Willing to return to Mayo Clinic enrolling institution for follow-up Willing to return to Mayo Clinic enrolling institution for follow-up Willing to return to Mayo Clinic in Rochester, Minnesota for follow-up Willingness to return to Mayo Clinic enrolling institution for follow-up ARM A: Willingness to return to Mayo Clinic in Arizona for follow-up ARM B: Willingness to return to Mayo Clinic in Arizona for follow-up Willingness to return to Mayo Clinic Rochester for follow up Willing to return to Mayo clinic for follow up Willing to return to Mayo Clinic for follow up Willing to return to Mayo Clinic for follow up Date of Mayo Clinic Genomics Tumor Board review =< 3 months prior to registration Willingness to return to Mayo Clinic Rochester for follow-up Willing to return to consenting Mayo Clinic (Mayo Clinic’s campus in Rochester), for follow-up during the Active Monitoring Phase of the study Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study and collect involved blood specimen prior to the start of radiation therapy, IRB number 15-000136. Willingness to return to Mayo Clinic Rochester for follow-up Willingness to return to Mayo Clinic Rochester for follow-up appointments Willing to return to Mayo Clinic Rochester for follow-up Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida for treatment\r\n* Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up Willing to return to consenting Mayo Clinic (Mayo Clinic’s campus in Rochester, Mayo Clinic’s campus in Arizona, or Mayo Clinic’s campus in Florida) institution for follow-up during the active monitoring phase of the study Willingness to return to Mayo Clinic Rochester for follow-up, except for some appointments that can be made with the local physician Willingness to return to Mayo Clinic Ability to provide informed consent, and to return to clinic for adequate follow-up for the period that the protocol requires Willingness to return to Mayo Clinic Rochester for follow-up Willing to receive their standard multimodality therapy at Mayo Clinic, Rochester Willing to return to Mayo Clinic, Rochester during the observation phase Willingness to return to Mayo Clinic for follow up Willing to return to Mayo Clinic enrolling institution for follow-up Willing to return to enrolling institution (Mayo Clinic in Arizona) for follow-up and all study treatments Computed tomography (CT) simulation, immobilization, MRI and PET imaging, treatment planning, and all follow-up MRI and PET scans to be performed at Mayo Clinic Rochester; Note: the actual radiation therapy treatments and follow-up other than imaging can be performed at Mayo Clinic Rochester, Northfield, LaCrosse, Mankato, Eau Claire, or Albert Lea Able to deliver four fresh (within 24 hours) stool samples to Mayo Clinic Rochester over a four month period