It’s important for an author to know their ultimate career goals. If your goal is to have a specific manuscript published by a Big 5 publisher, then it would be wise to sign with an agent first and have them submit the manuscript to those publishers. If you would like to be published by an indie press, then there is nothing wrong with querying those presses at the same time as agents. I would always suggest letting agents know as soon as an offer to publish comes in so that if an agent loves your writing, they can sign you and help you negotiate the offer and contract as needed.