The purpose of this study is to find the right dose of ONC206 that can be given safely to patients and to check whether the medication reaches the tumor tissue in the brain. The study is divided into different groups based on the type of tumor and previous treatments. Some patients will receive ONC206 alone, while others will receive it together with radiation therapy, which is a treatment that uses high-energy rays to target cancer cells. Some participants will receive ONC206 with a second course of radiation therapy if their tumor has grown back. There is also a part of the study that will measure how much of the medication gets into the tumor tissue by comparing it to the levels found in the blood before surgery.

During the study, patients will take ONC206 regularly and will have blood tests to check how the body processes the medication and to monitor for any side effects. Patients will also have imaging scans to see how the tumor responds to treatment. Some participants will need to provide tumor tissue samples that were collected during their standard medical care so researchers can study how the medication works in the tumor. The study will continue to monitor patients over time to gather information about safety and how well the treatment works.